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Background It remains unclear whether overall degree of immunosuppression or specific effects of individual immunosuppressive agents are causal for increased occurrence of BK polyomavirus ( BKPyV) infection in renal transplant recipients ( RTR). Methods A prospective, multicenter, open-label randomized controlled trial in 361 de novo RTR was performed. A total of 224 RTR were randomized at 6 months into three treatment groups with dual therapy consisting of prednisolone (Pred) plus either cyclosporine (CsA), mycophenolate sodium ( MPS), or everolimus ( EVL). Primary outcomes were incidence of BK viruria, BK viremia, and BKPyV-associated nephropathy ( BKVAN). Results From 6 months, incidence of BK viruria in the MPS group (43.6%) was significantly higher than in the other groups (CsA: 16.9%, EVL: 19.8%) ( P=.003). BKVAN was diagnosed in 3 patients, all treated with MPS (7.8%, P=.001). Longitudinal data analysis showed a lower BKPyV load and a significantly faster clearance of BK viruria in the CsA group compared to the MPS group ( P=.03). Conclusions Treatment with MPS was associated with an increased incidence of BK viruria. Dual immunosuppressive therapy with CsA and Pred was associated with the lowest rate of BKPyV replication and the fastest clearance of the virus. [ABSTRACT FROM AUTHOR]

Study Objective To investigate the influence of single nucleotide polymorphisms ( SNPs) in genes encoding metabolizing enzymes ( CYP2C8, CYP2J2, and UGT2B7) and transporters ( ABCC2 and ABCG2) on dose and dose-adjusted trough blood concentrations (C:D ratio), clinical outcomes, and occurrence of adverse events of tacrolimus and mycophenolate sodium in Brazilian kidney transplant recipients. Design Pharmacogenetic analysis of patients enrolled in a previously published study. Patients One hundred forty-eight adult kidney transplant recipients treated with tacrolimus, enteric-coated mycophenolate sodium, and prednisone for 90 days posttransplantation. Measurements and Main Results ABCC2 c.−24C>T and c.3972C>T, ABCG2 c.421C>A, CYP2C8*3, CYP2J2 c.−76G>T, and UGT2B7 c.372A>G SNPs were determined by real-time polymerase chain reaction. The CYP3A5*3C SNP data were used to eliminate the confounding effect of this variant on the results. ABCC2 c.3972T allele carriers showed higher tacrolimus C:D values than did carriers of the c.3972 CC genotype. The CYP2C8*3 variant was also associated with slightly higher tacrolimus C:D values and higher estimated glomerular filtration rate but only in CYP3A5-nonexpressing patients ( CYP3A5*3C/*3C carriers). None of the SNPs were associated with mycophenolate sodium dose or episodes of biopsy-confirmed acute rejection or delayed graft function. The CYP2J2 c.−76T allele was associated with increased risk for treatment-induced nausea and/or vomiting (OR: 5.30, 95% confidence interval 1.49-18.79, p<0.05). Conclusion The ABCC2 c.3972C >T polymorphism affected tacrolimus C:D in Brazilian kidney transplant recipients. Further, CYP2C8*3 and CYP2J2 c.−76G>T SNPs influenced the renal function of these patients and the occurrence of adverse events during treatment with tacrolimus and mycophenolate sodium. [ABSTRACT FROM AUTHOR]

The efficacy and safety of everolimus ( EVR) in simultaneous pancreas and kidney transplantation ( SPKT) is unclear. We retrospectively evaluated 25 consecutive SPKT recipients at our center from November 2011 to March 2013. All patients received dual induction (Thymoglobulin/basiliximab) and low-dose tacrolimus plus corticosteroids. Nine patients who received EVR were compared with 14 patients who received enteric-coated mycophenolate sodium ( EC- MPS); two patients who received sirolimus were excluded from the analysis. With a median follow-up of 14 months, the pancreas graft survival rate was 100% in both groups, and the kidney graft survival rate was 100% and 93% in EVR and EC- MPS patients, respectively. One EC- MPS patient lost her kidney graft from proteinuric kidney disease. Another EC- MPS patient received treatment for clinically diagnosed pancreas and kidney graft rejection. No rejection was observed in EVR patients. Serum creatinine and HbA1c levels were similar between the groups. There was no significant difference of surgical or medical complications. In conclusion, EVR seems to provide comparable short-term outcome to EC- MPS when combined with low-dose tacrolimus/steroids and dual induction therapy. A larger study with a longer follow-up is required to further assess this combination. [ABSTRACT FROM AUTHOR]

In the setting of liver transplantation, mycophenolate mofetil ( MMF) may be used as an adjuvant therapy for immunosuppression to prevent graft rejection; however, its use may be limited due to severe gastrointestinal ( GI) side effects. In contrast, enteric-coated mycophenolate sodium ( EC- MPS) may be associated with less severe side effects and hence better tolerability. We compared the side effects of EC- MPS to MMF in liver transplant patients in a de novo study (Study I-randomized, prospective, double-blinded) and a conversion study (Study II). In both studies, the severity of GI symptoms was assessed at various time points using the Gastrointestinal Symptoms Rating Scale ( GSRS) survey, a validated survey of GI symptoms (abdominal pain, reflux, indigestion, diarrhea, and constipation). In Study I, the symptoms of 30 recipients receiving EC- MPS (n = 15) were compared to 15 recipients receiving MMF. A multivariate analysis of variance ( MANOVA) of the total GSRS scores and symptom syndrome subscores revealed no significant difference (p > 0.05) between the two medications over time. A conversion study (Study II) with 29 participants, however, showed that over time, all GI symptoms improved significantly (p < 0.001) when the patients were treated with EC- MPS instead of MMF. [ABSTRACT FROM AUTHOR]

Aim: Mycophenolate is an immunosuppressive agent which has been used in systemic lupus erythematosus (SLE) patients who have failed conventional therapy. However, the use of mycophenolate sodium in extra-renal SLE involvement has yet to be established. This study aimed to assess the efficacy of mycophenolate sodium in extra-renal SLE. Methods: A total of 14 SLE patients without renal involvement were randomized either to receive mycophenolate sodium or other immunosuppressive agents. Patients were assessed monthly from baseline until week 16. Assessment parameters included SLE Disease Activity Index (SLEDAI) score, other organ-specific parameters and immunological parameters, including anti-double stranded DNA and C3. Steroid-sparing effect of mycophenolate sodium was also evaluated. Results: Mycophenolate sodium produced a significant reduction in SLEDAI scores (P < 0.05) after 16 weeks of treatment. Mixed responses were detected in terms of organ-specific clinical changes. A positive trend was observed in improvement of immunological parameters and steroid dose reduction. No major adverse events were reported in this study. Conclusion: Mycophenolate sodium is a safe alternative therapy in SLE patients with extra-renal involvement. The reduction in SLEDAI scores and the observation of no major safety concerns suggest that a larger prospective study of mycophenolate sodium in non-renal SLE is warranted. [ABSTRACT FROM AUTHOR]

Ricart MJ, Oppenheimer F, Andrés A, Morales JM, Alonso Á, Fernández C, on behalf of the Epi-trasplante Study, MIDATA Kidney-Pancreas Sub-study Group. Enteric-coated mycophenolate sodium in de novo and maintenance kidney-pancreas transplant recipients. Clin Transplant 2011 DOI: 10.1111/j.1399-0012.2011.01526.x. © 2011 John Wiley & Sons A/S. Abstract: Background: Our objective was to describe efficacy and safety of enteric-coated mycophenolate sodium (EC-MPS) in de novo and maintenance recipients of kidney-pancreas transplant in the clinical practice. Methods: Observational, multicentre, prospective, 12-month study. Results: We included 24 de novo and 24 maintenance patients. EC-MPS mean (±SD) doses at initiation in de novo patients were 1440 ± 0 vs. 1268 ± 263 mg/d at month 12 (M12). Patient and renal graft survival at one yr were 100%, and pancreatic graft survival was 83.3% (two losses owing to technical failure and two owing to rejection). In the maintenance cohort, EC-MPS was introduced at a median (P25-P75) of 30 (6-71) months after transplant. Baseline doses were 585 ± 310 vs. 704 ± 243 mg/d at M12. In this group, a significant increase in creatinine clearance was observed (65 ± 22 at baseline vs. 74 ± 20 mL/min at M12, p = 0.011). Patient, renal, and pancreatic graft survival were 100%, 95.8%, and 100%, respectively (one kidney graft loss owing to rejection). During follow-up, one patient from each group discontinued EC-MPS. Conclusions: The efficacy of EC-MPS in the clinical practice of kidney-pancreas transplantation is good, with high patient and grafts survival at 12 months, and good safety profile. The maintenance group displayed an improvement in renal function. [ABSTRACT FROM AUTHOR]

Background: The ideal treatment of lupus nephritis has yet to be defined. Both cyclophosphamide and mycophenolate mofetil have been used with encouraging results, but adverse events are frequently seen. There are no data on the use of enteric-coated mycophenolate sodium. Methods: We retrospectively reviewed 12 patients with active forms of lupus nephritis (1 class III, 7 class IV and 4 class V) treated with enteric-coated mycophenolate sodium combined with corticosteroids. Results: The mean age of the patients was 32.3 ± 11.2 years and the average length of follow up was 25.9 ± 8.9 months. The mean serum creatinine clearance was 93 ± 30.1 mL/min per 1.73 m2 and the mean proteinuria level was 4.5 ± 3.6 g/day. All had features that warranted aggressive treatment. Mycophenolate sodium was given for 12.9 ± 9.7 months with an averaged starting dose of 1350 ± 163 mg/day. Six patients attained complete remission and six attained partial remission with treatment. The mean interval to attain first remission (complete or partial) was 8.3 ± 5.7 weeks. At last follow up, all patients were in complete or partial remission. Apart from herpes zoster that developed in one patient, no other significant side-effects were encountered. Conclusion: Enteric-coated mycophenolate sodium was effective and well-tolerated in the treatment of active lupus nephritis. [ABSTRACT FROM AUTHOR]

Background Pemphigus is a chronic immunobullous disease, characterized by formation of blisters and erosions in skin and/or mucous membranes. This severe disease requires systemic immunosuppressive therapy. However, some patients are refractory, and long-term use of immunosuppressive agents can cause serious side-effects. Mycophenolic acid is increasingly being used as a corticosteroid-sparing agent or as monotherapy in immunosuppressive regimens. Objectives We aimed to evaluate the effectiveness of mycophenolate sodium, a sodium salt of mycophenolic acid, in the treatment of pemphigus vulgaris. Methods Six patients who were diagnosed as pemphigus vulgaris with active, refractory disease were treated with mycophenolate sodium. Three patients received mycophenolate sodium monotherapy; three patients received mycophenolate in combination with steroid. All patients were monitored regularly. Results Mycophenolate sodium was well tolerated with a similar efficacy of mycophenolate mofetil, and no side-effects have been observed. Conclusions Mycophenolate sodium appears to be an effective and safe alternative in the treatment of pemphigus vulgaris. [ABSTRACT FROM AUTHOR]